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Take Home Messages

` There is no physiological need for regular bleeding

when taking the COCP and withdrawal bleeding

confers no clinical benefits

` Extended cycling is useful in peri-menopausal

women with vasomotor symptoms during the

pill-free week, and for oestrogen-withdrawal

headaches at this time

DR TERRI FORAN MB BS (Syd), MClin Ed (UNSW), FAChSHM

Dr Terri Foran is a Sexual Health Physician with special interests in contraception, menopause issues and the

management of sexually transmitted infections. She is presently engaged in clinical and research work at

the Royal Hospital for Women in Sydney and also in clinical practice in an inner Sydney private practice. Terri

is currently the monthly Women’s Health columnist for Australian Doctor Magazine, and has contributed to

a 2011 Australian textbook on Sexual and Reproductive Health.

This article discusses the extended use of combined hormonal contraception and the research supporting it.

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Introduction

T he very early combined oral contraceptive pill (COCP) trials used continuous hormone administration, with the scheduled ‘pill-free-week’ introduced somewhat later in order to reduce the amount of irregular bleeding. At

the time the COCPs were first marketed, one of their proposed

advantages was that they provided a regular monthly bleeding

pattern that also reassured the user that she was not pregnant. In

the 1960s, the appearance of the next ‘menstrual’ bleed must have

provided an enormous sense of relief for women who, had until

that time, relied on much less effective contraceptive methods. This

original twenty-eight day pill cycle proved so successful that most

women now regard this as the ‘norm’, despite the fact that cycle

length is much more variable in real life. In fact, though 99% of

women of reproductive age have cycles from twenty-one to thirty-

five days,1 only 15% of those cycles are actually twenty-eight days

in length.1

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Extended Use of Combined Contraception

Why not Longer Cycles?

George Pincus, one of the scientists who developed the original oral contraceptive pill, acknowledged as early as 1958 that ‘a cycle of any desired length could presumably be produced,’2 although this is only possible on monophasic COCPs where all the active pills contain the same dose of oestrogen and progestogen. By the late 1960s, prolonged cycling of COCPs was already recommended by some gynaecologists as a useful treatment for endometriosis, dysmenorrhoea and heavy menstrual bleeding. The most common practice was to run three or four packets together, followed by a week-long break from active pills that allowed for withdrawal bleeding. This regimen was chosen since most monophasic pills can be used for three to four months without any break-through bleeding (BTB) whilst taking the active pills. The oestrogen component of the COCP is important, since adequate levels are required to stabilise the endometrium, but the degree of BTB seen in extended cycling of the COCP is largely dependent on the type and dose of progestogen. The choice of a progestogen that suppresses the endometrial lining to a greater extent potentially allows for longer extended cycling. Such progestogens include norethisterone, nomegestrol acetate, dienogest and gestodene. However, the actual length of time that bleeding can be suppressed varies greatly from woman to woman. There are some women who do not experience any bleeding at all, even after many months of extended cycling.

This has led to the concept of flexible or ‘menstrual-signalled’ cycling in which a woman is advised to take the COCP continuously until she experiences more than three days of bleeding. Studies indicate that if active pills are continued at this point, then bleeding is more likely to persist than to settle.3,4 A four-day break from active pills at that point, however, will initiate withdrawal bleeding. After that break, the woman can then resume the extended regimen until the next episode of significant BTB.

There is a long tradition in Australia of off-licence use of

many monophasic preparations for extended cycling

The concept of extended cycling of COCPs was formalised in the mid-2000s when four month and twelve month preparations were marketed in many countries. Australia presently has two licensed, extended COCPs, YAZ Flex® used in association with a dedicated reminder alarm and Seasonique,® a blister pack. These flexible preparations allows the user to manipulate her cycle length to suit her personal preference, ranging anywhere from twenty-eight to one hundred and twenty-four days. There is however a long tradition in this country of off-licence use of many monophasic preparations for extended cycling. One researcher noted in 2010 that around two-thirds of Australian students reported manipulating their COCPs to avoid regular bleeding.5

What Are the Potential Benefits of Extended Cycling of the Combined Pill?

Apart from the obvious advantages of lighter bleeding and reduced dysmenorrhoea, some researchers suggest that side-effects may actually occur more commonly during hormone-free days than during active treatment in a standard monthly COCP regimen.6 Extended cycling is also useful in peri-menopausal women who may experience vasomotor symptoms during the conventional pill-free week, and in those who experience oestrogen-withdrawal headaches at this time. There have been suggestions that extended cycling might be more effective than a conventional regimen, since an occasional missed pill is less likely to result in ovulation if it occurs during months of otherwise regular pill taking. However to date, though a number of trials have demonstrated equivalence in

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efficacy when extended-use COCPs are compared to conventional cyclical regimens,7,8 none have indicated superiority.

How Safe is Extended Cycling?

Women can be reassured that there is no physiological need for regular bleeding when taking the COCP and that withdrawal bleeding confers no clinical benefits. Prior to the registration of a twelve-month continuous regimen used in the United States in 2007, the manufacturer was required to demonstrate safety parameters equivalent to that of a conventional monthly COCP (fasting glucose, lipids, haemoglobin, blood pressure).9 A later study examining the extended use of a ethinyloestradiol/drospirenone preparation found no significant differences in lipid parameters, haemostatic variables or carbohydrate metabolism over two years use.10 A 2014 Cochrane review examined twelve trials of extended/continuous COCP use and concluded that the available evidence suggests that they are as safe as conventional regimens.11

Some women are also concerned that extended use of the COCP could have an adverse impact on their later fertility. Recent reviews, however, indicate a return to menses comparable to that seen with conventional COCP when used monthly. With either there is a median delay to return of ovulation of around thirty-two days.12,13

What Do Women Want?

Attitudes to menstrual bleeding are complex and influenced by culture. A review of several recent European studies indicated that the majority of women were open to reducing the frequency of vaginal bleeding episodes and approximately 30% of women indicated that they did not wish to have any bleeding at all.14

African-American women and those from Latin and Mediterranean backgrounds have generally expressed less enthusiasm for the concept of interfering with their monthly bleeding pattern,15,16 though this is less apparent when younger women in these groups are surveyed.16 Perhaps this is the point, that extended cycling will appeal to some women and not to others. Motivation for extended cycling of the COCP ranges all the way from a purely lifestyle choice to a means of controlling heavy or painful bleeding. The important thing is to ensure that such choices are available to women and that the clinical advice we provide is grounded in the best possible contemporary evidence.

Further Reading

Faculty of Sexual and Reproductive Health Care Clinical Guidance: Combined Contraception 2012. See section on Tailored Regimens- Item 3.2 https://www.fsrh.org/standards-and-guidance/documents/combined-hormonal-contraception/

Declaration

Dr Terri Foran was commissioned by Healthed for this article. The

ideas, opinions and information presented are solely those of the author. The advertiser does not necessarily endorse or support the views expressed in this article.

The author’s competing interests statement can be viewed at www.healthed.com.au/monographs.

References

1. Fritz M, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott Williams & Wilkins. 2010. p 241-242

2. Pincus G. The Control of Fertility. New York, London; Academic Press. 1965. p 219

3. Sulak PJ, Kuehl TJ, Coffee A et al. Prospective analysis of occurrence and management of breakthrough bleeding during an extended oral contraceptive regime. Am J Obstet Gynecol. 2006 Oct; 195(4): 935–41

4. Jensen JT, Garie SG, Trummer D et al. Bleeding profile of a flexible extended regimen of ethinylestradiol/drospirenone in US women: an open-label, three-arm, active-controlled, multicenter study. Contraception. 2012 Aug; 86(2): 110–118

5. Greig AJ, Palmer MA, Chepulis LM. Hormonal contraceptive practices in young Australian women (≤ 25 years) and their possible impact on menstrual frequency and iron requirements. Sex Reprod Healthc. 2010 Aug; 1(3): 99-103

6. Sulak PJ, Scow RD, Preece C et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol. 2000 Feb; 95(2): 261–66

7. Anderson FD, Hait H. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception. 2003 Feb; 68(2):89–96.

8. Archer DF, Jensen JT, Johnson JV et al. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec; 74(6):439–445

9. Archer DF, Jensen JT, Johnson JV et al. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec; 74(6):439–445

10. Klipping C, Duijkers I, Fortier MP et al. Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study. J Fam Plann Reprod Health Care. 2012 Apr; 38(2): 84-93

11. Edelman A, Micks E, Gallo MF et al. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014 Jul; (7): CD004695.

12. Barnhart K, Mirkin S, Grubb G et al. Return to fertility after cessation of a continuous oral contraceptive. Fertil Steril. 2009 May; 91(5): 1654–1656

13. Davis AR, Kroll R, Soltes B et al. Occurrence of menses or pregnancy after cessation of a continuous oral contraceptive. Fertil Steril 2008 May; 89(5): 1059-1063

14. Aubeny E. Are Monthly Menstrual Periods Optional?: A European Perspective. Reprod Health Matters 2007 May; 15(29): 183-185

15. Edelman A, Lew R, Cwiak C et al. Acceptability of contraceptive-induced amenorrhea in a racially diverse group of US women. Contraception. 2007 June; 75(6): 450-453

16. Sanchez-Borrego R, Garcia-Calvo C. Spanish women’s attitudes towards menstruation and use of a continuous, daily use hormonal combined contraceptive regimen. Contraception 2008 Feb; 77(2): 114-7

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